Multiple Treatments for Pneumonia

(REMAP-CAP Trial)

Recruiting at 395 trial locations

Overseen By Svenja Peters, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: MJM Bonten

Disqualifiers: Healthcare-associated pneumonia, Imminent death, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 21 days

20000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests various treatments for individuals with severe community-acquired pneumonia, particularly those in the ICU. It also examines treatments specifically for patients with COVID-19. Participants may receive different medications or treatment strategies to determine the most effective approach. Ideal candidates are those admitted to the ICU with pneumonia symptoms who require breathing support or medications to assist heart function. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to consult with the study team or your doctor for guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amoxicillin-clavulanate is generally safe for most people, with mild stomach issues as the most common side effect. Anakinra is also safe for long-term use, with mild injection site reactions being the most reported side effect. Studies suggest that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers might lower pneumonia risk and are safe for many patients. Apremilast has been used safely over long periods and is well-tolerated.

In trials, combining ARB with DMX-200 showed no major safety concerns. Aspirin is linked to lower death rates in pneumonia patients, but higher doses might cause stomach problems. Ceftaroline, used for pneumonia, has a safety profile similar to other antibiotics. Ceftriaxone is safe but can cause allergic reactions in some people.

Clopidogrel can increase pneumonia risk, though it is generally safe for long-term use. Blood thinners like therapeutic dose anticoagulation have mixed results, and high doses might not always be helpful. Convalescent plasma therapy showed varied safety results, depending on timing and patient condition.

Cysteamine is considered safe, with no new concerns in children. Eritoran is well-tolerated but hasn't shown significant survival benefits in severe infections. Extended use of macrolides for pneumonia is generally safe, with low treatment failure rates. Oseltamivir, an antiviral, is safe and can reduce pneumonia risks.

Fixed-dose hydrocortisone is safe but might not greatly reduce death rates in pneumonia. Hydroxychloroquine, alone or with lopinavir/ritonavir, has safety concerns like heart issues. Interferon beta-1a is safe but can cause flu-like symptoms and injection site reactions. Intermediate dose thromboprophylaxis is safe but needs more studies.

Ivermectin lacks strong evidence for pneumonia and might cause nerve issues. Lopinavir/ritonavir has safety concerns, including digestive issues. Macrolides are safe and effective for pneumonia. Moxifloxacin and levofloxacin are generally well-tolerated, though they can affect heart rhythms.

P2Y12 inhibitors, like ticagrelor, are linked to lower pneumonia risk and death rates. Piperacillin-tazobactam is safe but can cause serious skin reactions. Prasugrel is generally safe but hypersensitivity can occur. Sarilumab might cause serious infections.

Shock-dependent hydrocortisone is used safely in critical conditions. Simvastatin might reduce pneumonia risk and is safe. Tocilizumab increases infection risks but is generally safe for rheumatoid arthritis. Vitamin C is safe in high doses for severe pneumonia. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pneumonia because they offer a wide array of potential benefits that differ from standard care options. Unlike typical treatments that focus on antibiotics or supportive care, some investigational treatments like convalescent plasma and immunomodulators target the immune response, potentially enhancing recovery. Additionally, antiviral agents like lopinavir/ritonavir aim to directly reduce viral load, providing a different approach compared to traditional therapies. These unique mechanisms, along with diverse strategies like the use of vitamin C and endothelial modulators, highlight a comprehensive attempt to address pneumonia through multiple pathways, potentially leading to more effective and quicker recovery options.

What evidence suggests that this trial's treatments could be effective for pneumonia?

Research has shown that the antibiotic amoxicillin-clavulanate, which participants in this trial may receive, effectively treats community-acquired pneumonia, with one study reporting a 90.3% success rate. Another antibiotic, ceftaroline, is also under study in this trial and demonstrated an 81.2% success rate for all types of pneumonia. Tocilizumab, used for severe COVID-19 pneumonia, has improved patient outcomes and lowered death rates. Aspirin, part of a separate treatment arm, is linked to reduced death rates in pneumonia patients, while simvastatin, also studied in this trial, is associated with a 27% reduction in mortality. These treatments have strong evidence supporting their effectiveness in aiding pneumonia recovery. ^{1 6 7 8 9}

Who Is on the Research Team?

Lennie Derde, MD

Principal Investigator

UMC Utrecht, Coordinating Investigator REMAP-CAP Europe

John Marshall, Prof

Principal Investigator

Unity Health Toronto, Study Chair REMAP-CAP Canada

Derek Angus, Prof

Principal Investigator

University of Pittsburgh Medical Center, Study Chair REMAP-CAP USA

Marc Bonten, Prof

Principal Investigator

UMC Utrecht, Study Chair REMAP-CAP Europe

Colin McArthur, Dr

Principal Investigator

Medical Research Institute of New Zealand, Study Chair REMAP-CAP New Zealand

Steve Webb, Prof

Principal Investigator

Monash University, Study Chair REMAP-CAP Australia

Are You a Good Fit for This Trial?

This trial is for adults in ICU with severe community-acquired pneumonia, needing ventilators or vasopressors within 48 hours of hospital admission. It's also for those admitted with suspected or proven pandemic infection showing lower respiratory symptoms. Excluded are nursing home residents, recent REMAP participants, patients expected to die within 24 hours without full active treatment commitment, imminent discharges, and those hospitalized over 14 days for a pandemic illness.

Inclusion Criteria

It seems like "PLATFORM" is a bit vague. Could you please provide more context or clarify the term you are referring to?

I have symptoms like a cough or trouble breathing.

I was admitted to the ICU for severe pneumonia within 2 days of coming to the hospital.

Exclusion Criteria

Previous participation in this REMAP within the last 90 days

Healthcare-associated pneumonia: Prior to this illness, is known to have been an inpatient in any healthcare facility within the last 30 days

I've been in the hospital for over 14 days due to a suspected or confirmed pandemic illness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various randomized interventions for community-acquired pneumonia, including potential COVID-19 specific treatments

Up to 21 days

Daily monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including health-related quality of life assessment

6 months

Periodic assessments

Extension/Long-term follow-up

Participants may continue to be monitored for long-term outcomes such as multi-resistant organism colonisation and quality of life

Up to 90 days post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• Amoxicillin-clavulanate
• Anakinra
• Angiotensin converting enzyme inhibitor
• Angiotensin Receptor Blockers
• Apremilast
• ARB + DMX-200
• Aspirin
• Ceftaroline
• Ceftriaxone
• Clinician-preferred mechanical ventilation strategy
• Clopidogrel
• Continuation of therapeutic dose anticoagulation
• Convalescent plasma
• Conventional low dose thromboprophylaxis
• Cysteamine
• Delayed administration of convalescent plasma
• Eritoran
• Extended course macrolide
• Five-days oseltamivir
• Fixed-duration higher dose Hydrocortisone
• Fixed-duration Hydrocortisone
• Hydroxychloroquine
• Hydroxychloroquine + lopinavir/ritonavir
• Interferon beta-1a
• Interferon-β1a
• Intermediate dose thromboprophylaxis
• Ivermectin
• Local standard venous thromboprophylaxis
• Lopinavir/ritonavir
• Lopinavir / Ritonavir
• Macrolide administered for 3-5 days
• Macrolide administered for up to 14 days
• Moxifloxacin or Levofloxacin
• No antiplatelet
• No antiviral agent for COVID-19
• No antiviral agent for influenza
• No cysteamine
• No immune modulation for COVID-19
• No immunoglobulin
• No renin-angiotensin system inhibitor
• No simvastatin
• No systemic corticosteroid
• No vitamin C
• P2Y12 inhibitor
• Piperacillin-tazobactam
• Placebo
• Prasugrel
• Protocolised mechanical ventilation strategy
• Sarilumab
• Shock-dependent hydrocortisone
• Simvastatin
• Standard course macrolide
• Ten-days oseltamivir
• Therapeutic anticoagulation
• Ticagrelor
• Tocilizumab
• Vitamin C

Trial Overview REMAP-CAP evaluates various treatments to improve outcomes in patients with severe pneumonia in the ICU. It includes drugs like Hydroxychloroquine and Sarilumab among others, different ventilation strategies and doses of anticoagulants. The COVID-19 specific sub-platform tests additional interventions against the virus.

How Is the Trial Designed?

Group I: Vitamin C Domain Experimental Treatment 2 Interventions

Patients admitted to participating hospitals with community-acquired pneumonia will be randomised to receive no vitamin C, or vitamin C. Note: this domain is now closed.

Group II: Simvastatin Domain Experimental Treatment 2 Interventions

Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no simvastatin, or simvastatin. Note: this domain is now closed.

Group III: Mechanical Ventilation Domain Experimental Treatment 2 Interventions

Patients with community-acquired pneumonia admitted to participating intensive care units who are intubated and receiving invasive mechanical ventilation will be randomised to protocolised mechanical ventilation strategy, or clinician-preferred mechanical ventilation strategy

Group IV: Macrolide Duration Domain Experimental Treatment 2 Interventions

Patients with community-acquired pneumonia admitted to participating intensive care units who have been allocated to a beta-lactam antibiotic intervention in the Antibiotic Domain will be randomised to either a standard course or extended course of macrolide therapy

Group V: Influenza Immune Modulation Experimental Treatment 3 Interventions

Patients with community-acquired pneumonia admitted to participating intensive care units with microbiological testing confirmed influenza infection will be randomised to one of three interventions.

Group VI: Influenza Antiviral Domain Experimental Treatment 6 Interventions

Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.

Group VII: Immunoglobulin Domain Experimental Treatment 3 Interventions

Immunosuppressed patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive no immunoglobulin for COVID-19, or to receive high-titre convalescent plasma. Note: an earlier version of this domain was not restricted to immunosuppressed patients.

Group VIII: Endothelial Domain Experimental Treatment 2 Interventions

Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no endothelial modulator or enteral imatinib.

Group IX: Cysteamine Domain Experimental Treatment 2 Interventions

Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no cysteamine, or cysteamine. Note: this domain is now closed.

Group X: Corticosteroid Domain Experimental Treatment 5 Interventions

Patients with community acquired pneumonia (CAP) admitted to participating hospitals will be randomised to a steroid use strategy. Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19. Note: the fixed-course hydrocortisone has been closed to recruitment

Group XI: COVID-19 Immune Modulation Domain Experimental Treatment 5 Interventions

Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions. Note: this domain is now closed.

Group XII: COVID-19 Immune Modulation (2) Domain Experimental Treatment 3 Interventions

Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive one of three interventions. Note: this domain is now closed.

Group XIII: COVID-19 Antiviral Domain Experimental Treatment 5 Interventions

Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin. Note: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control. This domain is now closed.

Group XIV: COVID-19 Antiviral (II) Domain Experimental Treatment 4 Interventions

Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to one of up to four interventions.

Group XV: Antiplatelet Domain Experimental Treatment 3 Interventions

Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no antiplatelet, aspirin, or site-preferred P2Y12 inhibitor. Note: this domain is now closed.

Group XVI: Anticoagulation Domain Experimental Treatment 5 Interventions

Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy. Note: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation. This domain is now closed.

Group XVII: Antibiotic Domain Experimental Treatment 5 Interventions

Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions. Note: the ceftaroline + macrolide intervention has been closed to recruitment.

Group XVIII: ACE2 RAS Domain Experimental Treatment 4 Interventions

Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five renin-angiotensin system blockade strategies. Note: this domain is now closed.

Who Is Running the Clinical Trial?

MJM Bonten

Lead Sponsor

Trials

7

Recruited

37,900+

UMC Utrecht

Lead Sponsor

Trials

552

Recruited

2,124,000+

National University Hospital, Singapore

Collaborator

Trials

512

Recruited

7,394,000+

St. Marianna University School of Medicine

Collaborator

Trials

9

Recruited

22,400+

National Intensive Care Surveillance MORU

Collaborator

Trials

1

Recruited

20,000+

Unity Health

Collaborator

Trials

5

Recruited

22,900+

Berry Consultants

Collaborator

Trials

16

Recruited

58,200+

Intensive Care National Audit & Research Centre

Collaborator

Trials

15

Recruited

1,655,000+

Global Coalition for Adaptive Research

Collaborator

Trials

7

Recruited

22,600+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Published Research Related to This Trial

In a study of 180 children with acute otitis media, clarithromycin was found to be as effective as amoxicillin-clavulanate, with clinical improvement seen in 93% of patients receiving clarithromycin compared to 95% for amoxicillin-clavulanate within 4 days.

Clarithromycin demonstrated a favorable safety profile, with significantly fewer gastrointestinal side effects (20%) compared to amoxicillin-clavulanate (52%), making it a viable treatment option for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of the safety and efficacy of clarithromycin and amoxicillin-clavulanate in the treatment of acute otitis media in children. Aspin, MM., Hoberman, A., McCarty, J., et al.[2019]

Amoxicillin/clavulanate potassium extended release (ER) tablets are effective against common respiratory infections, including those caused by antibiotic-resistant bacteria, showing excellent success rates in clinical trials for acute bacterial sinusitis and community-acquired pneumonia.

This new formulation maintains therapeutic levels of amoxicillin for longer periods, enhancing its effectiveness against pathogens like Streptococcus pneumoniae and beta-lactamase-producing organisms, while being generally well tolerated by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxicillin/clavulanate potassium extended release tablets: a new antimicrobial for the treatment of acute bacterial sinusitis and community-acquired pneumonia. Benninger, MS.[2019]

Amoxicillin/clavulanic acid (Augmentin) is effective against common pathogens causing acute otitis media (AOM) in children, including penicillin-resistant strains, and has shown similar or better clinical response rates compared to other antibiotics in randomized trials involving pediatric patients aged 1 to 6 years.

The high-dose formulation of amoxicillin/clavulanic acid is well tolerated with a low incidence of adverse events (3.6%), making it a suitable treatment option for recurrent or persistent AOM, especially when resistant bacteria are suspected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxicillin/clavulanic acid: a review of its use in the management of paediatric patients with acute otitis media. Easton, J., Noble, S., Perry, CM.[2018]

In mouse models, clarithromycin was more effective than erythromycin against Streptococcus pneumoniae, showing better bacterial killing and survival rates when given as a single or two-dose regimen rather than multiple doses.

Erythromycin's efficacy improved with multiple doses that maintained serum concentrations above the minimum inhibitory concentration (MIC) for longer periods, highlighting the importance of dosing frequency and concentration in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo pharmacodynamic evaluation of clarithromycin in comparison to erythromycin. Novelli, A., Fallani, S., Cassetta, MI., et al.[2013]

In a study of 1174 patients with community-acquired pneumonia (CAP), the addition of clarithromycin to a β-lactam antibiotic significantly improved 28-day survival rates compared to other treatments, with a mortality rate of 20.8% for the clarithromycin group versus higher rates for azithromycin (33.8%), fluoroquinolone (32.3%), and β-lactam monotherapy (36.2%).

Clarithromycin also showed a higher resolution rate of CAP at 73.1%, compared to 65.9% for azithromycin, 58.5% for fluoroquinolone, and 61.5% for β-lactam, indicating its efficacy in treating severe cases of pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival benefit associated with clarithromycin in severe community-acquired pneumonia: A matched comparator study. Kyriazopoulou, E., Sinapidis, D., Halvatzis, S., et al.[2020]

In a study of 120 hospitalized patients, those receiving high doses of amoxicillin/clavulanate (10-12 g daily) were significantly more likely to have dangerously high INR values (≥ 4) compared to those on normal doses (up to 3.6 g daily), indicating a higher risk of over-anticoagulation when combined with warfarin.

The study found that an increased number of potentially interacting drugs not only raised the risk of high INR values but also increased the likelihood of bleeding episodes, highlighting the dangers of polypharmacy in patients on warfarin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate. Abdel-Aziz, MI., Ali, MA., Hassan, AK., et al.[2016]

Amoxicillin/clavulanate (Augmentin) has been effectively used for over 20 years to treat community-acquired respiratory tract infections, demonstrating high clinical efficacy against various bacteria, including those resistant to other antibiotics.

New high-dose formulations of amoxicillin/clavulanate have been developed to specifically target drug-resistant strains of bacteria, such as S. pneumoniae, while maintaining a strong safety profile similar to conventional formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent. White, AR., Kaye, C., Poupard, J., et al.[2022]

A 79-year-old man on warfarin for anticoagulation faced challenges in maintaining therapeutic levels after starting rifampin for osteomyelitis, requiring a 5- to 6-fold increase in his warfarin dose.

Discontinuing rifampin allowed for a gradual reduction in warfarin doses, highlighting the importance of careful monitoring and adjustment of anticoagulation therapy when these medications are used together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the interaction of rifampin and warfarin. Kim, KY., Epplen, K., Foruhari, F., et al.[2019]

In a study of 497 outpatients with acute maxillary sinusitis, clarithromycin was found to be as effective as amoxicillin/clavulanate, with clinical success rates of 97% and 93%, respectively.

Clarithromycin caused fewer gastrointestinal side effects compared to amoxicillin/clavulanate, with 41% of patients experiencing adverse events versus 46% in the amoxicillin/clavulanate group, suggesting it may be a better-tolerated option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of clarithromycin vs. amoxicillin/clavulanate in the treatment of acute maxillary sinusitis. Dubois, J., Saint-Pierre, C., Tremblay, C.[2013]

In a randomized trial involving 305 patients with mild COVID-19, adding either azithromycin or clarithromycin to standard care significantly improved symptoms like fever, dyspnea, and cough compared to standard care alone.

Both macrolides led to a quicker negative conversion of SARS-CoV-2 PCR results and improved chest CT findings after 2 weeks, suggesting they may enhance early recovery in mild COVID-19 cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of macrolides in management of patients with mild COVID-19. Rashad, A., Nafady, A., Hassan, MH., et al.[2022]

Clarithromycin showed the highest effectiveness against streptococci, making it a strong option for treating infections caused by these bacteria.

Cefprozil, cefuroxime, amoxicillin/clavulanate, and doxycycline were more effective against methicillin-susceptible Staphylococcus aureus and gram-negative bacteria like Klebsiella pneumoniae and Escherichia coli, indicating their potential as alternative treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of clarithromycin, cefprozil, and other common oral antimicrobial agents against gram-positive and gram-negative pathogens. Ritchie, DJ., Hopefl, AW., Milligan, TW., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10326520/

Effect of Angiotensin-Converting Enzyme Inhibitor and ... For the combined ARB and DMX-200 intervention, additional secondary safety outcomes included change from baseline to peak hepatic transaminases as well as ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02735707

Study Details | NCT02735707 | Randomized, Embedded, ... The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community- ...

3. investors.dimerix.com investors.dimerix.com/DownloadFile.axd?file=/Report/ComNews/20210423/02366351.pdf

COVID-19 STUDY INCORPORATING DMX-200 RECRUITS ... No significant adverse safety events were reported, and all study endpoints were achieved. The compelling results from this study prompted the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11499840/

Combination of the chemokine receptor type 2 (CCR2 ... A chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes ...

5. isrctn.com isrctn.com/ISRCTN67000769

An international platform trial for severely ill patients with ... The aim of this study is to generate evidence that can be used to reduce mortality (death), ICU resource use and morbidity (illness) in patients who are ...

6. investors.dimerix.com investors.dimerix.com/DownloadFile.axd?file=/Report/ComNews/20210924/02425712.pdf

DMX-200 RECOMMENDED FOR REGULATORY APPROVAL ... No significant adverse safety events were reported in any study, and all studies resulted in encouraging data that could provide meaningful ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02735707

Study Details | NCT02735707 | Randomized, Embedded, ... Olmesartan. Drug : ARB + DMX-200. Site-preferred ARB agent administered in combination with DMX-200 for 10 days or until hospital discharge, whichever occurs ...

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2803515

Effect of ACE Inhibitor and ARB Initiation on Organ Support ... For the combined ARB and DMX-200 intervention, additional secondary safety outcomes included change from baseline to peak hepatic ...

9. remapcap.eu remapcap.eu/wp-content/uploads/2021/04/R.-ACE2-RAS-V1.0.pdf

ACE2 Renin-Angiotensin System (RAS) Modulation Domain ARBs are considered safe in patients with prior ACEi- related angioedema (Rasmussen et al., 2019). Importantly, however, much of these safety data derives from ...